The intensive use of antibiotics has exerted a selective evolutionary pressure on micro-organisms to produce genetically based resistance mechanisms. Modern medicine and socio-economic behaviour exacerbates the problem of resistance development by creating slow growth situations for pathogenic microbes, e.g. in artificial joints, and by supporting long-term host reservoirs, e.g. in immuno-compromised patients.
In hospital settings, an increasing number of strains of Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp., and Pseudomonas aeruginosa, major sources of infections, are becoming multi-drug resistant and therefore difficult if not impossible to treat:                S. aureus is resistant to β-lactam and quinolone antibiotics and now even to vancomycin;        S. pneumoniae is becoming resistant to penicillin and quinolone antibiotics and even to new macrolides;        Enteroccocci are quinolone and vancomycin resistant and β-lactam antibiotics are inefficacious against these strains;        Enterobacteriacea are cephalosporin and quinolone resistant;        P. aeruginosa are β-lactam and quinolone resistant.        
Further new emerging organisms like Acinetobacter spp., which have been selected during therapy with the currently used antibiotics, are becoming a real problem in hospital settings.
In addition, microorganisms that are causing persistent infections are increasingly being recognized as causative agents or cofactors of severe chronic diseases like peptic ulcers or heart diseases.
WO 03/087098 discloses, among others, compounds of the general formula (A1)
wherein    one of Z1, Z2, Z3, Z4 and Z5 is N, one is CR1a and the remainder are CH, or one of Z1, Z2, Z3, Z4 and Z5 is CR1a and the remainder are CH;    R1 and R1a can notably be independently selected from hydrogen, halogen and C1-C6 alkoxy, provided that when Z1, Z2, Z3, Z4 and Z5 are CR1a or CH, then R1 is not hydrogen;    n is 0 or 1 and AB can notably represent a CR6R7—CR8R9 radical wherein each of R6, R7, R8 and R9 is independently selected from. H; (C1-6)alkoxy; (C1-6)alkylthio; halo; trifluoromethyl; azido; (C1-6)alkyl; (C2-6)alkenyl; (C1-6)alkoxycarbonyl; (C1-6)alkylcarbonyl; (C2-6)alkenyloxycarbonyl; (C2-6)alkenylcarbonyl; hydroxy, amino or aminocarbonyl which may be substituted; (C2-6)alkenylsulphonyl; or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6) alkyl or (C2-6)alkenyl; or R6 and R8 together represent a bond and R7 and R9 are as above defined;    R2 can be hydrogen, and    R4 can be a group —U—R52 in which R52 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A)
    containing up to four heteroatoms in each ring in which at least one of rings (a) and (b) is aromatic,    X1 is C or N when part of an aromatic ring or CR14 when part of a non aromatic ring;    X2 is N, NR13, O, S(O)x, CO or CR14 when part of an aromatic or non-aromatic ring or may in addition be CR14R15 when part of a non aromatic ring;    X3 and X5 are independently N or C;    Y1 is a 0 to 4 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring,    Y2 is a 2 to 6 atom linker group, each atom of Y2 being independently selected from N, NR13, 0, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring;    each R13 can notably be hydrogen;    each of R14 and R15 can notably be hydrogen;    each x is independently 0, 1 or 2;    U is CO, SO2 or CH2; or    R4 can also be a group —X1a—X2a—X3a—X4a wherein the group X1a—X2a—X3a can notably be CH2CH═CH or COCH═CH and X4a can notably be a phenyl substituted one to three times wherein the substituents are notably selected from halogen atoms;    which compounds of formula (A1) can be used as antibacterials.
WO 2004/002992 discloses, among others, compounds of the general formula (A2)
wherein    both rings (x) and (y) can be aromatic,    Z1 can be a 3 atom linker group each atom of which can be independently selected from N and CH,    Z2 can be a 3 atom linker group each atom of which can be independently selected from N and CH,    Z3 can be CH,    Z4 and Z5 can both be carbon atoms,    n is 0 or 1 and AB represents notably a CR6R7—CR8R9 radical wherein each of R6, R7, R8 and R9 is independently selected from. H; (C1-6)alkoxy; (C1-6)alkylthio; halo; trifluoromethyl; azido; (C1-6)alkyl; (C2-6)alkenyl; (C1-6)alkoxycarbonyl; (C1-6)alkylcarbonyl; (C2-6)alkenyloxycarbonyl; (C2-6)alkenylcarbonyl; hydroxy, amino or aminocarbonyl which may be substituted; (C2-6)alkenylsulphonyl; or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6) alkyl or (C2-6)alkenyl; or R6 and R8 together represent a bond and R7 and R9 are as above defined;    R2 can be hydrogen, and    R4 can be a group —U—R52 wherein U can be CH2 and R52 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A)
    containing up to four heteroatoms in each ring in which at least one of rings (a) and (b) is aromatic,    X1 is C or N when part of an aromatic ring or CR14 when part of a non aromatic ring;    X2 is N, NR13, O, S(O)x, CO or CR14 when part of an aromatic or non-aromatic ring or may in addition be CR14R15 when part of a non aromatic ring;    X2 is N, NR13, O, S(O)x, CO or CR14 when part of an aromatic or non-aromatic ring or may in addition be CR14R15 when part of a non aromatic ring;    Y1 is a 0 to 4 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring,    Y2 is a 2 to 6 atom linker group, each atom of Y2 being independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring;    each R13 can notably be hydrogen;    each of R14 and R15 can notably be hydrogen;    each x is independently 0, 1 or 2;    U is CO, SO2 or CH2;    R4 can also be a group —X1a—X2a—X3a—X4a wherein the group X1a—X2a—X3a can notably be CH2CH═CH or COCH═CH and X4a can notably be a phenyl substituted one to three times wherein the substituents are notably selected from halogen atoms;    which compounds of formula (A2) can be used as antibacterials.
It should however be noted that no specific example of compound of formula I as defined in this application is taught in WO 03/087098 or WO 2004/002992.
Besides, PCT application No. PCT/EP2005/010154 (published as WO 2006/032466 after the priority date of this application) discloses antibacterial compounds that are structurally similar to those of the instant invention, except the fact that they do not contain a cyclohexane-1,4-diyl motif but a cyclohexane-1,3-diyl, a tetrahydropyrane-2,5-diyl or a piperidine-2,5-diyl motif instead.